Endometrial cells in liquid-based cervical cytology: a diagnostic pitfall solved by preparing cytohistology from the residual thin layer sample.

OBJECTIVE: It was our aim to assess the usefulness of cytohistology in cervical thin layer brush samples with problems in the differential diagnosis of endometrial cells. STUDY DESIGN: This study reveals the cytological, cytohistological and immunohistochemistry findings of 8 cases suspicious of adenocarcinoma in situ (AIS)/adenocarcinoma (AC) in cervical liquid-based cytology (LBC) preparations that turned out to be normal endometrial cells. RESULTS: All 8 cervical LBCs featured endometrial and atypical endocervical-like columnar cells with frequent ragged 'feathered' edge appearance and rosette formations. Overlapping atypical glandular cell groups were present on 2 ThinPrep slides as well. In cytohistology of 7 cases, the recognition of endometrial stroma with endometrial glands easily allowed the diagnosis of normal endometrium. In 1 case with very small loose tissue fragments without glands, the diagnosis could be established by positivity for CD10 marker (endometrial stroma) and without proliferative activity in the Ki-67 immunostaining. CONCLUSION: In cervical LBC preparations, nuclear hyperchromasia, pleomorphism and nucleoli in normal endometrial cells are more obvious than in conventional smears, and their arrangement is sometimes suggestive of AIS or AC. In the 8 cases presented, we could avoid a false-positive diagnosis of AIS or AC through cytohistology/immunohistochemistry, and in consequence, unnecessary colposcopical/histological examination.

Increased diagnostic accuracy of atypical glandular cells in cervical liquid-based cytology using cell blocks.

OBJECTIVE: The purpose of this study was to reduce the number of diagnoses of atypical glandular cells (AGC). Residual material from the cervical ThinPrep® samples (Hologic, Marlboruogh, MA, USA) was used for cell blocks (CB) and immunohistochemistry (IHC). METHODS: In 2007 there were 87 patients (0.12% of tests) with AGC on liquid-based cytology (LBC) in the Leiden Cytology and Pathology Laboratory (LCPL) using the Bethesda System 2001 (TBS). CB with IHC was used for 26 of these cases. The vials still containing the brush (Cervex-Brush(®) Combi) were placed in a shaker for 10 minutes to dislodge the material trapped between the bristles. The residual sampling fluid was used to prepare paraffin sections (Shandon Cytoblock(®)) stained with Papanicolaou and immunostaining. RESULTS: Four of five cases with AGC not otherwise specified (NOS) were diagnosed with CB/IHC as benign mimics (endometrium, tubal metaplasia, follicular cervicitis, microglandular hyperplasia) and one of four with AGC-favour neoplasia (FN) (endocervical polyp). In one of five cases with AGC-NOS and in two of seven with AGC-FN, CIN3 was found on subsequent histological biopsy. Of six cases diagnosed as adenocarcinoma in situ (AIS) on LBC with CB/IHC the diagnosis was confirmed in four; one was adenocarcinoma and one glandular atypia. Of eight cases diagnosed as adenocarcinoma on cytology and CB/IHC, the diagnosis was confirmed in three. The other five cases were found to be one each of AIS, squamous cell carcinoma, CIN3, CIN2 with glandular atypia, and cervical endometriosis. CONCLUSIONS: By reducing the number of benign mimics of AGC, we achieved a high proportion (16/26; 61.5%) of neoplastic or preneoplastic lesions (glandular or squamous) on histological outcome potentially avoiding colposcopy. Histological biopsy verification by the gynaecologist is needed for final diagnosis of AGC-FN, AIS and adenocarcinoma.

Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy.

BACKGROUND: The ability of conventional CT scans and fiberoptic bronchoscopy to localize and properly stage radiographically occult lung cancer (ROLC) in the major airways is limited. High-resolution CT (HRCT) scanning and autofluorescence bronchoscopy (AFB) may improve the assessment of ROLC before the most appropriate therapy can be considered. PATIENTS AND METHODS: We prospectively studied 23 patients with ROLC, who were referred for intraluminal bronchoscopic treatment (IBT) with curative intent. Additional staging with HRCT and AFB was performed prior to treatment. Twenty patients were men, 9 patients had first primary cancers, and 14 patients had second primary cancers or synchronous cancers. RESULTS: HRCT scanning showed that 19 patients (83%) had no visible tumor or enlarged lymph nodes. With AFB, only 6 of the 19 patients (32%) proved to have tumors < or = 1 cm(2) with visible distal margins. They were treated with IBT. In the remaining 13 patients, abnormal fluorescence indicated more extensive tumor infiltration than could be seen with conventional bronchoscopy alone. Six patients underwent radical surgery for stage T1-2N0 (n = 5) and stage T2N1 (n = 1) tumors. Specimens showed that tumors were indeed more invasive than initially expected. The remaining seven patients technically did not have operable conditions, so they were treated with external irradiation (n = 4) and IBT (n = 3). The range for the time of follow-up for all patients has been 4 to 58 months (median, 40 months). The follow-up data underscore the correlation between accurate tumor staging and survival. CONCLUSIONS: Our data showed that 70% of patients presenting with ROLC had a more advanced cancer than that initially diagnosed, which precludes IBT with curative intent. Additional staging with HRCT and AFB enabled better classification of true occult cancers. Our approach enabled the choice of the most appropriate therapy for each individual patient with ROLC.

Addition of high-risk HPV testing improves the current guidelines on follow-up after treatment for cervical intraepithelial neoplasia.

We assessed a possible role for high-risk human papillomavirus (HPV) testing in the policy after treatment for cervical intraepithelial neoplasia (CIN) 2 or 3 (moderate to severe dysplasia). According to the Dutch guidelines follow-up after treatment consists of cervical cytology at 6, 12 and 24 months. Colposcopy is only performed in case of abnormal cervical cytology. In this observational study 184 women treated for CIN 2 or 3 were prospectively monitored by cervical cytology and high-risk HPV testing 3, 6, 9, 12 and 24 months after treatment. Post-treatment CIN 2/3 was present in 29 women (15.8%). A positive high-risk HPV test 6 months after treatment was more predictive for post-treatment CIN 2/3 than abnormal cervical cytology (sensitivity 90% and 62% respectively, with similar specificity). At 6 months the negative predictive value of a high-risk HPV negative, normal smear, was 99%. Largely overlapping, partly different groups of women with post-treatment CIN 2/3 were identified by HPV testing and cervical cytology. Based on these results we advocate to include high-risk HPV testing in monitoring women initially treated for CIN 2/3. In case of a high-risk HPV positive test or abnormal cervical cytology, colposcopy is indicated. All women should be tested at 6 and 24 months after treatment and only referred to the population-based cervical cancer screening programme when the tests are negative on both visits.

PCR based high risk HPV testing is superior to neural network based screening for predicting incident CIN III in women with normal cytology and borderline changes.

BACKGROUND/AIMS: To improve the accuracy of conventional cytology in cervical cancer screening, high risk human papillomavirus (HPV) testing and neural network based screening have been developed. This study assessed the power of both techniques to detect women at risk of developing incident CIN III; that is, CIN III detected during the follow up of women with normal cytology and borderline nuclear changes. METHODS: A cohort of 2250 women, 34-54 years of age, who attended population based cervical cancer screening from 1988 to 1991 and had normal smears or borderline nuclear changes was followed. All smears were tested for high risk HPV and the smears were rescreened using neural network based screening. The value of neural network based screening for predicting incident CIN III during a mean follow up period of 6.4 years was compared with that of high risk HPV testing. In addition, morphological markers presumed to be related to HPV were correlated with HPV status. RESULTS: Thirteen (0.6%) women had incident CIN III. Both high risk HPV positivity and abnormal cytology were associated with an increased risk for incident CIN III (odds ratio, 240 and 22, respectively) and high risk HPV positivity was associated with abnormal cytology. The sensitivity of high risk HPV testing for predicting incident CIN III was much higher than that of neural network based screening (92% and 46%, respectively). None of the morphological markers assessed, including koilocytosis, was correlated with high risk HPV status. CONCLUSION: High risk HPV testing is superior to neural network based screening in identifying women at risk of developing CIN III. For women with normal cytology and borderline changes and a negative high risk HPV test, the screening interval can be considerably prolonged.

Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study.

BACKGROUND: A relation has been established between infection with high-risk types of human papillomavirus and development of cervical cancer. We investigated a role for testing for human papillomavirus as part of cervical-cancer screening. METHODS: We monitored by cytology, colposcopy, and testing for high-risk human papillomavirus 353 women referred to gynaecologists with mild to moderate and severe dyskaryosis. The median follow-up time was 33 months. At the last visit we took biopsy samples. Our primary endpoint was clinical progression, defined as cervical intraepithelial neoplasia (CIN) 3, covering three or more cervical quadrants on colposcopy, or a cervical-smear result of suspected cervical cancer. FINDINGS: 33 women reached clinical progression. All had persistent infection with high-risk human papillomavirus. The cumulative 6-year incidence of clinical progression among these women was 40% (95% CI 21-59). In women with end histology CIN 3, 98 (95%) of 103 had persistent infection with high-risk human papillomavirus from baseline. Among women with mild to moderate dyskaryosis at baseline, a second test for human papillomavirus at 6 months predicted end histology CIN 3 better than a second cervical smear. INTERPRETATION: Persistent infection with high-risk human papillomavirus is necessary for development and maintenance of CIN 3. All women with severe dyskaryosis should be referred to gynaecologists, whereas women with mild to moderate dyskaryosis should be referred only after a second positive test for high-risk human papillomavirus at 6 months.

Telomerase activity exclusively in cervical carcinomas and a subset of cervical intraepithelial neoplasia grade III lesions: strong association with elevated messenger RNA levels of its catalytic subunit and high-risk human papillomavirus DNA.

In this study, we investigated telomerase activity and human telomerase reverse transcriptase (hTERT) mRNA expression in relation to high-risk human papillomavirus (HPV) DNA presence in the spectrum of cervical premalignant lesions. Reconstruction experiments revealed that telomerase activity determined by the telomeric repeat amplification protocol assay and hTERT mRNA by reverse transcriptase-PCR could be detected in down to 100 and 1 SiHa cervical cancer cells, respectively. Telomeric repeat amplification protocol analysis on cervical tissue specimens revealed that none of the histomorphologically normal cervical samples (n = 8) and cervical intraepithelial neoplasia (CIN) grade I (n = 10) and grade II (n = 8) lesions had detectable telomerase activity. However, telomerase activity was shown in 40% of CIN grade III lesions (n = 15) and 96% of squamous cell carcinomas (n = 24). Despite the fact that hTERT mRNA was found at much higher frequencies, semiquantitative reverse transcriptase-PCR revealed that elevated hTERT mRNA levels were strongly correlated with detectable telomerase activity. Furthermore, telomerase activity and elevated hTERT mRNA levels were only detected in cases that contained high-risk HPV DNA. In contrast, low or undetectable hTERT mRNA levels were demonstrated in both high-risk HPV positive and negative cases. These data indicate that telomerase activity detectable with the assay used and concomitant elevated levels of hTERT mRNA reflect a rather late step in the CIN to squamous cell carcinoma sequence, which follows infection with high-risk HPV.

Well-differentiated papillary mesothelioma of the peritoneum: a separate entity.

Three female patients with a diffuse well-differentiated papillary mesothelioma of the peritoneum are presented. They did not have a history of exposure to asbestos. The peritoneal biopsies were studied extensively, including electron microscopy, nuclear morphometry and DNA ploidy analysis. The results from these more sophisticated investigations confirmed the mesothelial origin and further characterised these lesions. One of the 3 patients has continuing elevated serum CA-125 levels, which increased transiently during and after pregnancy. All 3 patients have done well without therapy, 2 patients being alive and non-symptomatic 6 and 7 years after the initial diagnosis. It is important to distinguish this disorder from the malignant diseases of the peritoneum and the ovary. In view of the indolent course of this subtype of mesothelioma, avoidance of treatment is justified unless there is evidence of progressive disease.

Chlamydia trachomatis and ectopic pregnancy: retrospective analysis of salpingectomy specimens, endometrial biopsies, and cervical smears.

AIMS: To examine the role of Chlamydia trachomatis in ectopic pregnancy by detection of DNA in archival salpingectomy specimens, and in their preceding cervical specimens and endometrial biopsies, by using the polymerase chain reaction (PCR). METHODS: Archival paraffin embedded salpingectomy tissues (n = 48) from 37 women with ectopic pregnancy were examined for the presence of C trachomatis plasmid and omp1 DNA by PCR. In addition, preceding cervical specimens (n = 58) stored either as cervical cell suspensions or as archival cervical smears, and preceding endometrial biopsies (n = 18), taken 0-5.8 years before the ectopic pregnancy, were examined by PCR for the presence of C trachomatis. RESULTS: C trachomatis DNA was detected in only one of the 48 salpingectomy specimens from 37 women. However, in six of the 37 women, C trachomatis DNA was detected in the genital specimens (cervix and/or endometrial) taken before salpingectomy. C trachomatis infections were mostly found in endometrial or cervical specimens taken more than three years before ectopic pregnancy. No chlamydial DNA was found in endometrial or cervical specimens taken at the same time of the ectopic pregnancy. CONCLUSIONS: Although no C trachomatis DNA was found in salpingectomy specimens, several women with ectopic pregnancy had C trachomatis infections in endometrial and cervical specimens in the past. This suggests that at least in these cases the ectopic pregnancy is a late post-inflammatory complication of an ascending C trachomatis infection resulting in a scarred fallopian tube.

Human papillomavirus in false negative archival cervical smears: implications for screening for cervical cancer.

AIM: To assess the value of detecting human papillomavirus (HPV) DNA in false negative archival cervical smears in population based screening programmes for cervical cancer. METHODS: Cytomorphologically classified false negative archival Pap smears (n = 27) taken from 18 women up to six years before cervical cancer was diagnosed were blindly mixed with 89 smears from hospital patients with a variety of gynaecological complaints and tested for HPV by the polymerase chain reaction (PCR). Corresponding cervical cancer biopsy specimens were also available for HPV analysis. Neither the examining cytopathologist nor the molecular biologist was aware of the study design. RESULTS: HPV DNA was detected in the smears of 16 patients with cervical cancer missed previously by cytology. HPV 16 and 18 were found predominantly in those smears taken up to six years before the diagnosis of cervical cancer. The smears of the two remaining patients were reclassified as inadequate for cytology or contained no suitable DNA for PCR. In 15 patients the same HPV type could be found in the smears and the cervical cancer biopsy specimens. CONCLUSIONS: The results indicate that high risk HPV types can be detected in archival smears classified as false negative on cytology and that cytological screening errors may be reduced if combined with PCR testing for HPV.

The presence of persistent high-risk HPV genotypes in dysplastic cervical lesions is associated with progressive disease: natural history up to 36 months.

To evaluate the clinical significance of HPV genotyping for the prediction of progressive cervical intraepithelial neoplasia (CIN) in women with cytomorphologically abnormal smears, a prospective, blind, non-intervention study was performed. A total of 342 patients screened with cytomorphologically abnormal cervical smears were monitored every 3-4 months by cervical cytology, colposcopy and HPV testing using PCR. Women with progressive CIN disease were defined as patients developing lesions with a colposcopic impression of CIN III over more than 2 quadrants or resulting in a cytological smear equivalent to Pap 5. These patients were subsequently treated according to standard procedures. If any doubt arose about the true status of the patients (n = 75) these patients were censored and biopsied. The mean follow-up time was 16.5 months (range 3-36 months). Nineteen women showed progressive CIN disease and all appeared to be continuously HPV-positive from the start of the study. At biopsy, all these patients were histologically classified as CIN III. Seventeen of these women were positive for high-risk HPV types. Two cases were classified as still unidentified HPV. No progression was seen in the absence of HPV DNA or in the presence of low-risk HPV types. In life-table analysis the cumulative rate of progressive, histologically verified CIN disease was 17% after 36 months. Further analyses showed that other risk factors such as age, sexarche, number of sexual partners or smoking hardly influenced the effect of HPV on progression. The results show that the continuous presence of high-risk HPV types in women with cytomorphologically abnormal smears is a strong marker for progressive CIN disease.

Neuroendocrine neoplasms of the larynx. Importance of the correct diagnosis and differences between atypical carcinoid tumors and small-cell neuroendocrine carcinoma.

Findings in the present study have confirmed that the diagnosis of neuroendocrine tumors of the larynx (NETL) requires that a panel of neuroendocrine markers and electron microscopy be performed. This means that the clinician must be aware of the clinical presentations of such patients and should send fresh biopsy specimens to the clinical laboratory for optimal tissue studies. As shown in this study, the possibility of misdiagnosis of an atypical carcinoid tumor (ACT) is rather high. In establishing a diagnosis, a part of the material should be fixed for conventional histology, a part for immunohistochemistry and a part for electron microscopy. The correct diagnosis of NETL is obviously of great importance for subsequent treatment and prognosis. Patients with the diagnosis of ACT of the larynx require surgical treatment. Our findings also show that small-cell neuroendocrine carcinomas of the larynx should be considered to be a disseminated disease at initial presentation. A metastatic workup is necessary, but radical surgical procedures should be avoided. The combination of radiotherapy and chemotherapy is always indicated.

Free vascularized jejunum interposition for pharyngoesophageal reconstruction after total laryngopharyngectomy.

The records of 28 patients who underwent free jejunal graft reconstruction after resection for cancer involving the pharynx were analysed. Seven patients had a T3 carcinoma, 15 patients T4 and six patients recurrence after laryngectomy. Ten patients had received radiotherapy in the past. Post-operatively, 15 patients (54%) had complications and two patients (7%) died. No significant difference was observed in the complication rate between the group that received radiotherapy in the past and those who did not. Nineteen patients received post-operative radiotherapy. Nine patients had no radiotherapy on the basis of complete resection or because of serious complications. For the whole group the 2-year recurrence free period and survival were 42% and 51% respectively. The post-operative radiotherapy group had a significantly better survival (73%) and recurrence free period (63%) than the group without post-operative radiotherapy (0%). Thus, post-operative radiotherapy seems indicated irrespective of resection margins.

Analysis of cytomorphologically abnormal cervical scrapes for the presence of 27 mucosotropic human papillomavirus genotypes, using polymerase chain reaction.

The aim of this study was to investigate the distribution of 27 mucosotropic human papillomavirus (HPV) genotypes (HPV 6, 11, 13, 16, 18, 30, 31, 32, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61 and 66) in cytomorphologically abnormal cervical scrapes (Pap IIIa-Pap IV; n = 1,373) using the polymerase chain reaction (PCR) method on crude cell suspensions. The scrapes were analyzed for the presence of HPV DNA by HPV general-primer-mediated PCR (GP-PCR), which allows the detection of a broad spectrum of HPV types at the subpicogram level. Subsequently, 2 HPV typing procedures based on either type-specific PCR (for HPV 6, 11, 16, 18, 31 and 33) or characterization of GP-PCR products by hybridization (for HPV 13, 30, 32, 35, 39, 40, 43, 44, 45, 51, 52, 53, 54, 55, 56, 57, 58, 59, 61 and 66) were applied. Increasing total HPV prevalence was found with increasing severity of dysplasia from 71% in Pap IIIa to 100% in Pap IV scrapes (carcinoma in situ). The scrapes which were positive by type-specific PCR included 47% cases of Pap IIIa, 71% cases of Pap IIIb and 90% cases of Pap IV. Moreover, 12% of Pap IIIa scrapes, 6% of Pap IIIb scrapes and 8% of Pap IV scrapes revealed positivity for one or more of the remaining HPV types, as determined by successive hybridizations of the GP-PCR products. Taking the typing data together, we noted that the level of HPV heterogeneity decreased from 22 different HPV types (HPV 6, 11, 16, 18, 31, 33, 35, 39, 40, 42, 43, 44, 45, 51, 52, 54, 55, 56, 58, 59, 61 and 66) detected in the group of Pap IIIa scrapes to 13 (HPV 6, 11, 16, 18, 31, 33, 35, 45, 51, 52, 58, 59 and 61) and 10 HPV genotypes (HPV 6, 16, 18, 31, 33, 45, 51, 52, 54 and 58) in the Pap IIIb and Pap IV classes, respectively. An increasing prevalence rate from Pap IIIa to Pap IV was found for HPV 16, 18, 31, 33, 45 and 54. The prevalence rate of identified HPV genotypes increased from 59% in Pap IIIa to 98% in Pap IV, indicating that almost all high-risk HPV genotypes related to cervical cancer in The Netherlands have been characterized.

Prevalence of HPV in cytomorphologically normal cervical smears, as determined by the polymerase chain reaction, is age-dependent.

The prevalence of human papillomavirus (HPV) genotypes in relation to age was investigated by the polymerase chain reaction (PCR) method in cytologically normal smears from 4 different groups of women. Group A consisted of young women from a district population, aged 15-34 years, using oral contraceptives and visiting general practitioners for a check-up (n = 156); group B were asymptomatic women, aged 35-55, in a district population participating in a triennial screening program for cervical cancer (n = 1555); group C and D consisted of women, seen at the gynecological outpatient department for a wide spectrum of gynecological complaints or for control of their hormonal contraception, aged 15-34 years (n = 2320), and aged 35-55 years (n = 1826) respectively. An HPV (all types) prevalence of 14.1%, 4.1%, 13.9% and 6.6% and an HPV 16/18 prevalence of 3.8%, 0.9%, 3.3% and 1.5% were found in groups A, B, C and D respectively. Statistically significant differences (p value < 0.001) in HPV prevalence were found between women aged 15-34 years and women aged 35-55 years in the district population and in the hospital population. No statistically significant differences in HPV 16/18 were observed after age-matching between women in corresponding age-classes of both populations. In a 5-year interval analysis a strong age-dependent relationship was demonstrated, with a maximum between 20 and 24 years. After the age of 35 a constant level of 1-2% HPV 16/18 was observed. These results indicate that genital HPV infections are age-dependent and suggest that HPV infections at young age can be transient. The implications of these findings in the context of cervical cancer screening are discussed.

The contribution of immunocytochemistry in diagnostic cytology. Comparison and evaluation with immunohistology.

This study reports on the use and evaluation of immunocytochemistry in diagnostic cytology by correlation with (immuno)histology. The cytologic material was collected during a period of 3 years. Sixty-four patients were selected and studied retrospectively. The reactivity of a number of polyclonal and monoclonal antibodies was investigated and applied to a diverse group of tumors. Marker expression on routine cytologic and histologic material was compared and the use of immunocytochemistry in diagnosis was evaluated. Immunocytochemistry proved to be an easy and valuable technique for the identification and classification of tumor cells, and there was a good concordance with immunohistology. A discrepancy in marker expression was found in 10% of the slides that were investigated. Immunocytochemistry led to a misdiagnosis in only four cases; however, in these cases cytology alone would not have led to the correct diagnosis. The causes for the discrepancies are discussed. It is estimated that immunocytochemistry contributed to the diagnosis of approximately 50% of the cases, supplying either additional or essential information. A wide variety of markers can be applied reliably on cytologic preparations. The use of panels of antibodies is mandatory.

Endocervical curettage by Vabra aspiration as part of colposcopic evaluation.

Endocervical curettage as routine part of colposcopic examination in patients with abnormal cervical cytology is recommended by many experts. Endocervical curettage (ECC) by Vabra aspiration has never been reported in literature. The results of Vabra ECC in 103 patients are analyzed and compared to the results of a second endocervical specimen, obtained by conventional curettage, cone biopsy, or hysterectomy. An accordance of over 98% is demonstrated and the difference is discussed. In 88% and 71% adequate Vabra ECC specimens were available for cytological and histological examination, respectively. In any patient at least one result was present. Both cytological and histological specimens are of reliable quality. No cases of invasive (adeno)carcinoma were missed. In addition, the results are compared to literature data concerning Vabra aspiration for endometrial disease and ECC by other techniques. Vabra ECC is considered an efficient, safe, and well-tolerated diagnostic outpatient method and recommended as a standard part of colposcopic evaluation.

A study of the importance of fine needle aspiration cytology in the diagnosis of the solitary thyroid nodule.

The results of 287 fine needle aspirations (FNAs) of the thyroid, performed between 1 January 1982 and 31 December 1986, were retrospectively analysed with respect to clinical history, physical examination, scintigraphy and echoscopy, and compared with the results of the histological examination of thyroid tissue removed from the 65 patients who were operated. Except for the follicular tumour group, FNA examination proved to be the best method for differentiating benign and malignant lesions. The specificity was found to be 48%, the sensitivity 86%. The only value of scintigraphy and echoscopy appears to be in their supporting role. Based on these results a new strategy for the evaluation of thyroid nodules is proposed, in which the FNA examination has a more important place in the diagnosis than before.